Antimalarial β-Carbolines from the New Zealand Ascidian Pseudodistoma opacum

One tetrahydro-β-carboline, (−)-7-bromohomotrypargine (1), and three alkylguanidine-substituted β-carbolines, opacalines A, B, and C (2–4), have been isolated from the New Zealand ascidian Pseudodistoma opacum. The structures of the metabolites were determined by analysis of mass spectrometric and 2D NMR spectroscopic data. Natural products 2 and 3, synthetic debromo analogues 8 and 9, and intermediate 16 exhibited moderate antimalarial activity toward a chloroquine-resistant strain of Plasmodium falciparum, with an IC50 range of 2.5–14 μM. The biosynthesis of 1–4 is proposed to proceed via a Pictet–Spengler condensation of 6-bromotryptamine and the α-keto acid transamination product of either arginine or homoarginine. Cell separation and 1H NMR analysis of P. opacum identified tetrahydro-β-carboline 1 to be principally located in the zooids, while fully aromatized analogues 2–4 were localized to the test.